CRESEMBA 40 mg HARD CAPSULES

Introduction

Package Leaflet: Information for the Patient

Cresemba, Hard Capsules 40mg

Cresemba, Hard Capsules 100mg

isavuconazonium

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Cresemba and what is it used for
2. What you need to know before you take Cresemba
3. How to take Cresemba
4. Possible side effects
5. Storage of Cresemba
6. Contents of the pack and other information

1. What is Cresemba and what is it used for

What is Cresemba

Cresemba is an antifungal medicine that contains the active substance isavuconazonium.

How Cresemba works

Isavuconazonium works by killing or stopping the growth of the fungus that causes the infection.

What Cresemba is used for

Cresemba is used in adults and pediatric patients from 6 years of age to treat the following fungal infections:

• invasive aspergillosis, caused by a fungus of the 'Aspergillus' group,
• mucormycosis, caused by a fungus belonging to the 'Mucorales' group, in patients for whom treatment with amphotericin B is not appropriate.

2. What you need to know before you take Cresemba

Do not take Cresemba

• if you are allergic to isavuconazonium or any of the other ingredients of this medicine (listed in section 6),
• if you have a heart rhythm problem called 'short QT syndrome',
• if you are taking any of the following medicines:
  • ketoconazole, used for fungal infections,
  • high doses of ritonavir (more than 200 mg every 12 hours), used for HIV,
  • rifampicin, rifabutin, used for tuberculosis,
  • carbamazepine, used for epilepsy,
  • barbiturates such as phenobarbital, used for epilepsy and sleep disorders,
  • phenytoin, used for epilepsy,
  • St. John's Wort, a herbal medicine used for depression,
  • efavirenz, etravirine, used for HIV,
  • nafcillin, used for bacterial infections.

Warnings and precautions

Talk to your doctor or pharmacist or nurse before you start taking Cresemba:

• if you have had an allergic reaction to another antifungal treatment with 'azole', such as ketoconazole, fluconazole, itraconazole, voriconazole, or posaconazole in the past,
• if you have severe liver disease. Your doctor should monitor you for possible side effects.

Monitoring of side effects

Stop taking Cresemba and call your doctor immediately if you notice any of the following side effects:

• sudden wheezing, difficulty breathing, swelling of the face, lips, mouth, or tongue, intense itching, sweating, dizziness, or fainting, rapid heartbeat or palpitations in the chest: these may be signs of a severe allergic reaction (anaphylaxis).

Changes in liver function

Cresemba may sometimes affect liver function. Your doctor may perform blood tests while you are taking this medicine.

Skin problems

Call your doctor immediately if you experience severe skin peeling, mouth, eyes, or genital areas.

Children and adolescents

Do not give Cresemba capsules to children between 1 and less than 6 years of age, as this medicine has not been studied in this age group. For children from 6 years of age and adolescents with a body weight of at least 32 kg, your doctor may prescribe Cresemba 100 mg capsules. Other forms of the medicine are more suitable for children or adolescents who cannot swallow capsules; consult your doctor or pharmacist.

Other medicines and Cresemba

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines. Some medicines may change the way Cresemba works or Cresemba may change the way other medicines work if taken at the same time.

In particular, do not take this medicine and tell your doctor or pharmacist if you are taking any of the following medicines:

• ketoconazole, used for fungal infections,
• high doses of ritonavir (more than 200 mg every 12 hours), used for HIV,
• rifampicin, rifabutin, used for tuberculosis,
• carbamazepine, used for epilepsy,
• barbiturates such as phenobarbital, used for epilepsy and sleep disorders,
• phenytoin, used for epilepsy,
• St. John's Wort, a herbal medicine used for depression,
• efavirenz, etravirine, used for HIV,
• nafcillin, used for bacterial infections.

Unless your doctor tells you otherwise, do not take this medicine and tell your doctor or pharmacist if you are taking any of the following medicines:

• rufinamide or any other medicine that reduces the QT interval on the electrocardiogram (ECG),
• aprepitant, used to prevent nausea and vomiting in cancer treatment,
• prednisone, used for rheumatoid arthritis,
• pioglitazone, used for diabetes.

Tell your doctor or pharmacist if you are taking any of the following medicines, as it may be necessary to adjust or monitor the dose to ensure that the medicines continue to have the desired effect:

• cyclosporine, tacrolimus, and sirolimus, used to prevent transplant rejection,
• cyclophosphamide, used for cancer,
• digoxin, used to treat heart failure or irregular heartbeat,
• colchicine, used to treat gout attacks,
• dabigatran etexilate, used to prevent blood clots after hip or knee replacement surgery,
• clarithromycin, used for bacterial infections,
• saquinavir, fosamprenavir, indinavir, nevirapine, lopinavir/ritonavir combination, used for HIV,
• alfentanil or fentanyl, used for severe pain,
• vincristine, vinblastine, used for cancer,
• mycophenolate mofetil (MMF), used in transplant patients,
• midazolam, used for severe insomnia and stress,
• bupropion, used for depression,
• metformin, used for diabetes,
• daunorubicin, doxorubicin, imatinib, irinotecan, lapatinib, mitoxantrone, topotecan, used for different types of cancer.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine.

Do not take Cresemba if you are pregnant, unless your doctor tells you otherwise. As it is not known whether it can affect or harm the fetus.

Cresemba should not be used during breastfeeding.

Driving and using machines

Cresemba may make you feel confused, tired, or drowsy. It may also cause fainting. Therefore, be very careful when driving or operating machinery.

3. How to take Cresemba

Follow the instructions for administration of this medicine exactly as indicated by your doctor or pharmacist. If you are unsure, consult your doctor or pharmacist again.

The recommended dose is as follows:

Use in children and adolescents

The use of Cresemba 100 mg capsules has not been studied in children and adolescents. Your doctor may prescribe Cresemba 100 mg capsules to children and adolescents with a body weight of at least 32 kg.

Other forms of the medicine are more suitable for children or adolescents who cannot swallow capsules; consult your doctor or pharmacist.

You should take this dose until your doctor tells you otherwise. The duration of treatment with Cresemba may be more than 6 months, if your doctor considers it necessary.

The capsules can be taken with or without food. Swallow the capsules whole. Do not chew, crush, dissolve, or open the capsules.

If you take more Cresemba than you should

If you take more Cresemba than you should, talk to a doctor or go to the hospital immediately. Take the medicine package with you to show the doctor what you have taken.

It may cause more side effects such as:

• headache, feeling dizzy, agitation, or drowsiness,
• tingling, decreased sensitivity, or tactile sensation,
• problems perceiving things, hot flashes, anxiety, joint pain,
• altered taste, dry mouth, diarrhea, vomiting,
• palpitations, increased heart rate, increased sensitivity to light.

If you forget to take Cresemba

Take the capsule as soon as you remember. However, if it is almost time for the next dose, skip the missed dose.

Do not take a double dose to make up for the missed doses.

If you stop taking Cresemba

Do not stop taking Cresemba unless your doctor has told you to. It is important to continue treatment with this medicine until your doctor tells you to. This is to ensure that the fungal infection has disappeared.

If you have any other questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Stop taking Cresemba and call your doctor immediately if you notice any of the following side effects:

• a severe allergic reaction (anaphylaxis) such as sudden wheezing, difficulty breathing, swelling of the face, lips, mouth, or tongue, intense itching, sweating, dizziness, or fainting, rapid heartbeat or palpitations in the chest.

Call your doctor immediately if you notice any of the following side effects:

• severe skin peeling, mouth, eyes, or genital areas.

Other side effects

Tell your doctor, pharmacist, or nurse if you notice any of the following side effects:

Common:may affect up to 1 in 10 people

• reduced potassium levels in the blood,
• decreased appetite,
• confusion (delirium),
• headache,
• drowsiness,
• inflamed veins that can cause blood clots,
• sudden shortness of breath or severe respiratory problems,
• nausea, vomiting, diarrhea, and stomach pain,
• changes in blood tests of liver function,
• skin rash, itching,
• kidney failure (symptoms may include swelling of the legs),
• chest pain, feeling tired or drowsy.

Uncommon:may affect up to 1 in 100 people

• reduced white blood cell count, may increase the risk of infection and fever,
• reduced platelet count, may increase the risk of bleeding or bruising,
• reduced red blood cell count, may make you feel weak or short of breath or pale,
• severe reduction in the number of blood cells, may make you feel weak, cause bruising, or increase the likelihood of infections,
• skin rash, swelling of the lips, mouth, tongue, or throat with difficulty breathing (hypersensitivity),
• low blood sugar levels,
• low magnesium levels in the blood,
• low levels of a protein called 'albumin' in the blood,
• malnutrition,
• low sodium levels in the blood (hyponatremia),
• depression, difficulty sleeping,
• stroke, fainting, or feeling faint, dizziness,
• tingling, numbness, or prickling sensation in the skin (paresthesia),

• alterations in mental status (encephalopathy),
• altered taste (dysgeusia),
• 'spinning' sensation or dizziness (vertigo),

• heart rhythm problems, may be too fast, or irregular, or extra heartbeat, this may appear on your electrocardiogram or ECG,
• circulatory problems,
• low blood pressure,
• wheezing, rapid breathing, coughing up blood or bloody sputum, nosebleeds,
• indigestion,
• constipation,
• abdominal distension (bloating),
• enlarged liver,
• liver inflammation,
• skin problems, red or purple spots on the skin (petechiae), skin inflammation, hair loss,
• back pain,
• swelling of the limbs,
• feeling weak, very tired, drowsy, feeling unwell (malaise).

Side effects with unknown frequency:

• anaphylaxis (a severe allergic reaction).

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if it is possible side effects not listed in this leaflet. You can also report side effects directly through the national reporting system included in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Cresemba

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the label after EXP. The expiry date is the last day of the month indicated.

Do not store above 30°C.

Store in the original packaging to protect from moisture.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Cresemba

• The active substance is isavuconazole. Each capsule contains 74.5 mg of isavuconazonium sulfate, equivalent to 40 mg of isavuconazole (for Cresemba 40 mg hard capsules) or 186.3 mg of isavuconazonium sulfate, equivalent to 100 mg of isavuconazole (for Cresemba 100 mg hard capsules).
• The other ingredients are:
• Capsule content: magnesium citrate (anhydrous), microcrystalline cellulose (E460), talc (E553b), colloidal anhydrous silica, stearic acid.
• Capsule shell for Cresemba 40 mg hard capsules: hypromellose, red iron oxide (E172), titanium dioxide (E171).
• Capsule shell for Cresemba 100 mg hard capsules: hypromellose, red iron oxide (E172) (only in the capsule body), titanium dioxide (E171), gellan gum, potassium acetate, disodium edetate, sodium lauryl sulfate.
• Printed ink: shellac (E904), propylene glycol (E1520), potassium hydroxide, black iron oxide (E172).

Appearance of Cresemba and Package Contents

Cresemba 40 mg hard capsules are brown-red capsules with the cap marked with “CR40” in black ink.

Cresemba 100 mg hard capsules are capsules with the brown-red body marked with “100” in black ink and a white cap marked with "C" in black ink.

Cresemba 40 mg hard capsules are available in boxes with 35 capsules. Each box contains 7 aluminum blisters with 5 capsules each.

Cresemba 100 mg hard capsules are available in boxes with 14 capsules. Each box contains 2 aluminum blisters with 7 capsules each.

Each capsule is connected to a bag with a ‘desiccant’ to protect the capsule from moisture.

Do not puncture the blister with the desiccant.

Do not ingest or use the desiccant.

Marketing Authorization Holder:

Basilea Pharmaceutica Deutschland GmbH

Marie-Curie-Strasse 8

79539 Lörrach

Germany

Manufacturer:

Almac Pharma Services (Ireland) Limited

Finnabair Industrial Estate

Dundalk

Co. Louth

A91 P9KD

Ireland

Almac Pharma Services Limited

Seagoe Industrial Estate

Craigavon, Co. Armagh

BT63 5UA

United Kingdom (Northern Ireland)

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

Date of the Last Revision of this Prospectus:

Other Sources of Information

Detailed information about this medication is available on the European Medicines Agency website: https://www.ema.europa.eu. There are also links to other websites about rare diseases and orphan medicines.